Defensins at the Interface of Male and Female Innate Immunity

男性和女性先天免疫界面的防御素

• 批准号: 0843649
• 负责人: Gary Cherr
• 金额: $ 52.99万
• 依托单位: University of California-Davis
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2014-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0843649&HistoricalAwards=false
• 关键词: Defensins; Interface; Male; Female; Innate

Gary N CherrIOS-0843649Defensins at the Interface of Male and Female Innate ImmunityThe mammalian female reproductive tract has immune responses to protect against foreign invaders, including the attraction of white blood cells to the area. How sperm cells overcome these defenses as well, and at the same time, play a role in white blood cell attraction, are key questions in reproductive biology. The central hypothesis of this grant seeks to link these two important steps of mammalian reproduction into a unifying concept. The investigators have recently demonstrated that molecules called beta-defensins uniformly coat the entire surface of mammalian sperm during maturation in the male tract. Beta-defensins are key effector peptides of innate immunity found throughout the animal kingdom. These peptides have potent antimicrobial activities and act as chemical attractants. While the expression of beta-defensin peptides by reproductive tissue has been described in several invertebrate species, the presence of beta-defensins on the sperm surface is a novel finding and has only been recently described in mammals. Their presence may reflect adaptations of these peptides for internal fertilization. It is proposed that sperm-associated beta-defensins, which form a uniform surface coat on spermatozoa, promote fertility by first protecting sperm from immunorecognition by the female reproductive tract and then providing enhanced innate immune protection in part by attracting white blood cells. The investigators propose to test these ideas through a combination of in vivo and in vitro experiments using a mouse model. This innovative project will yield answers to longstanding questions in reproductive biology and will provide insights into the sources of variation of reproductive fitness in mammals. The understanding of these mechanisms holds significance for managing reproduction in domestic species, evaluating reproductive fitness in wildlife, and maintaining reproductive health in humans.

Gary N CherrIOS-0843649男性和女性先天免疫界面的防御素哺乳动物女性生殖道具有免疫反应来防御外来入侵者，包括吸引白细胞到该区域。 精子细胞如何克服这些防御，同时在白细胞吸引中发挥作用，是生殖生物学的关键问题。 该资助的中心假设旨在将哺乳动物繁殖的这两个重要步骤连接成一个统一的概念。 研究人员最近证明，在雄性生殖道成熟过程中，称为β-防御素的分子均匀地覆盖在哺乳动物精子的整个表面。 β-防御素是整个动物界中发现的先天免疫的关键效应肽。 这些肽具有有效的抗菌活性，并可作为化学引诱剂。 虽然已经在几种无脊椎动物物种中描述了生殖组织表达β-防御素肽，但精子表面上β-防御素的存在是一个新发现，并且最近才在哺乳动物中进行描述。它们的存在可能反映了这些肽对体内受精的适应。 有人提出，精子相关的β-防御素在精子上形成均匀的表面涂层，首先保护精子免受女性生殖道的免疫识别，然后部分通过吸引白细胞来提供增强的先天免疫保护，从而促进生育能力。 研究人员建议通过使用小鼠模型进行体内和体外实验相结合来测试这些想法。 这个创新项目将为生殖生物学中长期存在的问题提供答案，并将提供对哺乳动物生殖适应性变异来源的见解。 了解这些机制对于管理家养物种的繁殖、评估野生动物的繁殖适应性以及维护人类的生殖健康具有重要意义。